Brand name: Combivir

Generic name: lamivudine/zidovudine, or 3TC/AZT

Class: Nucleoside reverse transcriptase inhibitor (nucleoside, NRTI, or nuke) -- fixed dose combination

Manufacturer: ViiV Healthcare,, (877) 844-8872

AWP: $1,081.70/month

Standard Dose: One tablet (150 mg lamivudine/300 mg zidovudine) twice a day (12 hours apart), with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Should not be used in children weighing less than 66 pounds, nor in people with kidney function less than 50 mL/min or those with liver disease because the dose cannot be adjusted with this fixed dose combination. Generic is available.

Potential side effects and toxicity: See the individual drugs contained in Combivir, Epivir, and Retrovir, for details. Fatigue, myopathy (muscle damage), and flare-up of hepatitis B upon stopping (due to the withdrawal of lamivudine). The zidovudine in Combivir has been associated with alteration of various cells in the blood through bone marrow suppression, resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss of the arms, legs, face, and/or buttocks -- sometimes called "AZT butt"). The lipoatrophy could be irreversible or fat could take a long time to rebuild after your regimen is changed. See chart for potential drug class side effects.

Potential drug interactions: Also see the individual drugs contained in Combivir, Epivir, and Retrovir, for more information. Do not take Combivir with Atripla, Complera, Emtriva, Epivir, Epivir-HBV, Epzicom, Retrovir, Trizivir, or Truvada, since all or part of these medications are already in Combivir or they have equivalent medications. Zerit cannot be taken with Combivir, as it can limit effectiveness of the zidovudine part of Combivir.

More information: May be taken with food to decrease potential nausea associated with zidovudine. One head-to-head study against Truvada (emtricitabine and tenofovir) found greater toxicity with Combivir, due to anemia (see Retrovir). Last year, the HIV treatment guidelines from the Department of Health and Human Services (DHHS) downgraded Combivir from "alternative" to "acceptable" dual nuke background for people taking antiviral therapy for the first time, citing twice-daily dosing and greater toxicity than Truvada or Epzicom. Anyone taking zidovudine might consider taking Combivir even if you are already resistant to the lamivudine component. Resistance to lamivudine makes HIV less fit to replicate. It also slightly improves the antiviral activity of zidovudine and tenofovir (Viread), and for that reason, some doctors keep lamivudine onboard in combination with those drugs after M184V resistance develops. Thanks to extensive data, Combivir continues to be preferred to Truvada for pregnant women who are taking therapy for the first time, according to the treatment guidelines. See package insert for more complete information on potential side effects and interactions.

Doctor's Comments

In the early years of the HAART era, Combivir was the most commonly used nucleoside "backbone" in what was often referred to as the "cocktail." Since then it's lost its luster: it's taken twice a day and has the disadvantages of zidovudine (AZT) toxicity (see Retrovir). As a result, it's been largely replaced by the safer and better tolerated once-daily co-formulations, Truvada and Epzicom. Because the patents have expired on both AZT and 3TC (Epivir), Combivir is now available in generic form, but who cares?

-- Joel Gallant, M.D., M.P.H.

Activist's Comments

Although no longer the backbone of choice, Combivir represents a pivotal point in the history of regimens: fewer pills, less often, fewer side effects (for most folks). This set the tone for future regimens to ease up on the pill burdens, and a focus on finding less toxic formulas. It's still quite useful in prevention of mother-to-child transmission in many parts of the world. Combivir can still be a good backup plan for those unable to take other nucleoside backbones, so it continues to have a place in the antiretroviral arsenal, but is clearly not a major player in the future of HIV treatment.

-- Joey Wynn

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